Analysis Of Immunogenicity Effect And Safety Of Tetravalent Measles, Mumps, Rubella And Varicella Vaccine

[Background]Measles,mumps,rubella and varicella are viral infections which can implicate seriously long-term sequelae of infected individuals or even the unborn child,people are generally susceptible with them.Vaccines against the individual diseases have long been available,and significantly reduced the incidence and mortality of related diseases.Today vaccinations against measles,mumps,rubella and varicella are now carried out mainly with combination vaccines.Combined vaccine not only improves the compliance of the vaccinees,but also helps to reduce a series of problems such as vaccine management.Tetravalent measles,mumps,rubella and varicella(MMRV)was originally designed as an alternative to separate measles-mumps-rubella(MMR)vaccine and varicella(V)vaccine,based on similar vaccination schedules,and was listed abroad from 2005 in USA,but as the first measles containing vaccine(MCV),the immunogenicity and safety of MMRV remains controversial.[Objective]To evaluate the immunogenicity effect and safety of MMRV versus MMR with or without varicella(MMR+V/MMR)in healthy children aged 9-24 months as the first measles containing vaccine(MCV).To describe the immunogenicity and safety ofMMRV take with other vaccines at the same time.To preliminarily explore the advantages and disadvantages of MMRV vaccine as the first dose of MCV vaccine.[Methods]Searching "National Center for Biotechnology Information,NCBI"," Cochrane Library,CL":Random control trials(RCT)for comparing immunogenicity effect and safety between MMRV and MMR+V/MMR were included,and Meta-Analysis were made by Stata11.0 software.Pooled relative risk(RR)with 95%confident interval(CI)was calculated to assess the antibody seroconversion rate(ASR)against specific antigens and the incidence of adverse event(AE)after vaccination.Literatures for MMRV co-administered with other vaccines were retrieved to describe the difference between ASR of MMRV with or without other vaccines.[Results](1)A total of 14 studies were included for MMRV vs MMR+V.MMRV and MMR+V showed comparable immunogenicity effects against measles,mumps,rubella and varicella[RRmeasles=1.00(95%CI:0.99-1.00),Z=0,98,P>0.05;RRmumps=0.98(95%CI:0.98-1.00),Z=1.72,P>0.05;RRrubella=1.00(95%CI:1.00-1.01),Z=0.72,P>0.05;RRvaricella=0.98(95%CI:0.95-1.00),Z=1.70,P>0.05].MMRV showed significantly higher incidence of fever and rash than MMR+V[RRfever=1.19(95%CI:1.08-1.32),Z=3.62,P<0.01;RRrash=1.28(95%CI:1.10-1.49),Z=3.16,P<0.01],while MMRV and MMR+V showed comparable incidence rate against redness and pain[RRredness=1.04(95%CI:0.94-1.16),Z=0.72,P>0.05;RRpain=0.94(95%CI:0.85-1.04),Z=1.21,P>0.05].No obvious publication bias were found according to the Egger’s test,(P all>0.05).(2)A total of 4 studies were included for MMRV vs MMR.Compared with MMR,MMRV showed comparable immunogenicity effects against measles and rubella[RRmeasles=1.01(95%CI:1.00-1.02),Z=1.23,P>0.05;RRrubella=1.01(95%CI:1.00-1.01),Z=1.13,P>0.05],lower immunogenicity effects against mumps[RRmumps=0.96(95%CI:0.94-0.99),Z=2.63,P<0.01],higher incidence of fever[RRfever=1.28(95%CI:1.17～1.41),Z=5.14,P<0.01],and comparable incidence rate of rash,redness and pain[RRrash=0.91(95%CI:0.60-1.38),Z=0.45,P>0.05;RRredness=1.04(95%CI:0.94-1.16),Z=1.89,P>0.05;RRpain=0.94(95%CI:0.91-1.06),Z=1.80,P>0.05].No obvious publication bias were found according to the Egger’s test,(P all>0.05).(3)A total of 5 studies describe the difference between ASR of MMRV with or without other vaccines at the same visit.The immunogenicity effects of MMRV to measles,mumps,rubella and varicella were not affected when MMRV co-administered with diphtheria-tetanus-acellular pertussis vaccine(DTaP),inactivated poliovirus(IPV),hepatitis B vaccine(HepB),haemophilus influenzae type b vaccine(Hib),pneumococcal 7-valent conjugate vaccine(PCV-7),tetravalent meningococcal serogroups A,C,W-135 and Y conjugate vaccine(ACWY-TT),meningococcal serogroups C vinnce(Men C),hepatitis A vaccine(HAV)and so on.[Conclusions]The immunological effect of MMRV and MMR+V/MMR vaccines are comparable,however,MMRV shows higher incidence rates of generalized reactions.The immunological effect of MMRV was not significantly affected when MMRV co-administered with other vaccine.The advantages and disadvantages of MMRV as the first dose of MCV vaccination remain to be discussed.